hyponatremia. manisha sahay why hyponatremia important ? common electrolyte abnormality- inpatient...
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Hyponatremia
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Manisha sahay
Why hyponatremia important ?
Common electrolyte abnormality- inpatient and outpatient
Up to 15 % of inpatients 1
Acute-• 8.4% in childen• 55% in adults
• Chronic• 14-27%
1. Baylis PH. Int J Biochem Cell Biol. 2003;35:1495-1499.
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Manisha sahay
Important cause of mortalityMortality more if hyponatremia develops after
hospitalisationIncreased duration of hospital stayIncreased mortality continues even after dischargeEven mild hyponatremia though till now
considered benign is associated with osteoporosis and fractures
Adrogué HJ. Am J Nephrol. 2005;25:240-249Gill ,clin endocrino 2006Clayton ,QJM 2006European Jr of Endocrinology,2010
Manisha
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Manisha sahay
Definition of Hyponatremia
Normal serum sodium level
: 135 – 145mEq/L
Hyponatremia is defined as a serum sodium level less than 135mEq/L
Severe - serum Na < 120mEq/L
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SYMPTOMS
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Manisha sahay
Clinical ManifestationsClinical Manifestations
Hyponatremia not a disease but a manifestation of a variety of disorders.
Clinical symptoms hyponatremia itself
Disease causing hyponatremia recognition of hyponatremia incidental.
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Acute
Low serum Na More Na in brain
Water enters brain cells
Cerebral oedema
Chronic
Adaptation
Pathogenesis
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Manisha sahay
S [Na] > 125 mmol/Lor
Gradual onset
AsymptomaticGI sym
HeadacheLethargy
ConfusionObtundation
Stupor Seizures
ComaRhabdomyolysis
Brain stem compressiomPulm oedema
Na+ level <120mEq/Lor
Rapid decrease(<48hr)
Symptoms depend onmagnitude of the hyponatremia rapidity of its development.
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Manisha sahay
Symptoms & signs
Gait disturbancesFractures
• reduction in total hip bone mineral density of 0.037 g/cm2 for every 1 mmol/l drop in plasma sodium concentration.
European Jr Endocrinology 2010
Manisha Sahay
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Etiology -Hyponatremia
HyperglycemiaMannitol
Hyperlipidemia
Hyperproteinemia
SIADHGC defHypothyroidExercise indPsychogenic
CHFNSCirrhosis
CRFGI loss3rd space loss
Salt wasting dzRTADiureticsCerebral salt wasting
?? ?
??
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Manisha sahay
Determine if true Hyponatremia?
IA Pseudohyponatremia/Normal plasma osmolality
(275-295)
1. Hyperlipidemia - ion-specific electrodes avoid thision-specific electrodes avoid this
2. Hyperproteinemia-Multiple myeloma
IB Increased plasma osmolality /Translocational/redistributive
(osmo > 295)A. Hyperglycemia 1.6 mEq/L for every 100 mg/dL [glucose)1.6 mEq/L for every 100 mg/dL [glucose)
B. Mannitol
II. Hypoosmolal hyponatremia (serum osmolality<275mOsm/kg)
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Manisha sahay
Hypovolemic
Hypervolemic
Euvolemic
2 stepcheck volume status
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Hypovolemic- Low CVP Responds to NS
Low urine Na(<20 mmol/l)
Non renal • Volume Depletion
• GI, lung or skin losses -burns
• Third space sequestration
• CSW • Excess water
intake
High urine Na >20 mmol/l
Renal• Salt wasting
nephropathy• Mineralocorticoid
deficiency-high K• Osmotic diuresis-
KB• Cerebral salt
wasting
Manisha Sahay
Step 3
Check renal or non renalUrine Na
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Diuretics
Thiazides Urine excreted- NS Lose more salt than loop Reason for hypoNa
• Interfere with urine dilution
Common in elderly females
Occurs within 2-4 weeks
Discontinue diuretics
Loop Diuretics Urine excreted 1/2 NS
Lose > water than thiazides
Reason for hypoNa:• Impair generation of
medullary hypertonicity
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Manisha sahay
Cerebral Salt Wasting Causes: Head injury, surgery, tumors, Infections Signs/symptoms:
• Polyuria, Dehydration/hypovolemia/Hypotension• High urine Na > 20 mmol/L
Pathogenesis: renal Na loss d/t plasma ANP, BNP • Volume depletion could be protective for ICP
Treatment:• Volume replacement - large volumes of NS• Oral Na supplementation for a period of time
Berendes Lancet 1997, Isotani Stroke 1994, Wijdicks Stroke 1991
Mather J Neuro Nsurg Psych 1981; Wijdicks Ann Neuro 1985
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Manisha sahay
TreatmentHypovolemic hyponatremia
Isotonic saline Restoration of euvolemia removes the
hemodynamic stimulus for AVP release Excretion of the excess free water
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Manisha sahay
Hypovolemic
Hypervolemic Euvolemic
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Hypervolemic -High CVP Increased total body water that exceeds the increase in total body Na+
Low urine Na <20 mmol/l
•CHF•Cirrhosis with
ascites• Nephrotic
syndrome
High urine Na >20 mmol/l
•Advanced renal failure
Manisha Sahayin
Step 3Check urine Na
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Manisha sahay
TreatmentHypervolemic hyponatremia
Restriction of Na+ and water intake Promotion of water loss in excess of Na+Vasopressin antagonists approved for use Correction of underlying disorder
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Manisha sahay
Hypovolemic
Hypervolemic Euvolemic
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Manisha sahay
Euvolemic – Normal CVP
Normal sodium stores (N ECF) & total body excess of free water.
SIADH/Reset osmostat Primary polydipsiaHypothyroidismGlucocorticoid deficiencyExercise inducedBeer potomaniaPost op
Step 3
All have high urine NaU osm <100 in PP, BP
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SIADH (Bartter’s Criteria)60% of all euvolemic hyponatremia F
Essential criteria Hyponatremia pl osm<275 Euvolemia clinical u osmolality > 200
mOsm/kg N renal, cardiac, hepatic,
adrenal, pituitary, thyroid No H/o antidiuretic drugs No emotional or physical
stress Urinary sodium > 20 mEq/l Cr N, N ABG, K+ handling
Supplemental features uric acid<4BUN<10 failure to correct
hypoNa after NS infusion
correction of hypoNa after fluid restriction
S ADH
Step 4
Check urine osmolalityK/Cr/ Cr/Urea/uric acidT3/T4/TSHCortisolCT as needed
U SP gravity can be used if u osm not possible, U osm 100= u sp gr 1.005
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Disorders associated with SIADH
PulmonaryPulmonary abscessTuberculosisAspergillosisPositive-pressure breathingAsthmaPneumothoraxCystic fibrosisLung cancers
CancersSmall cell carcinoma of the lungCarcinoma of the duodenumCarcinoma of the pancreasThymomaLymphomaEwing’s sarcomaMesotheliomaCarcinoma of the bladderProstatic carcinomaOlfactory neuroblastoma
CNS-ADH secrEncephalitis /Meningitis , traumaBrain abscess/Brain tumorsGBS/Acute intermittent porphyriaSubarachnoid/subdural hematomaCerebellar and cerebral atrophyCavernous sinus thrombosisNeonatal hypoxiaHydrocephalusDelirium tremensCVA, Acute psychosisPeripheral neuropathyMultiple sclerosis
PULMONARY
CANCERS
CNS
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SIADHSIADH CSWCSWCNS problemCNS problem yesyes yesyes
Urine NaUrine Na High (renal)High (renal) High (renal)High (renal)
Urine osmUrine osm High >100 mosm/kgHigh >100 mosm/kg < 100 mosm/kg< 100 mosm/kg
Urine OutputUrine Output decreaseddecreased polyuricpolyuric
CVPCVP High (Euvolemic)High (Euvolemic) Low (Hypovolemic)Low (Hypovolemic)
BUNBUN N or ↓BUN ↑BUN
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Manisha sahay
DRUGSDRUGSAntidiuretic hormones:Antidiuretic hormones: Vasopressin,oxytocinDiuretics:Diuretics: Thiazides,furosemide, CNS-active drugs:CNS-active drugs: Vincristine,carbamazepine, Psychotropic drugs Inhibitors of prostaglandinInhibitors of prostaglandin Chlorpropamide, Salicylates,Acetaminophen, NSAIDS,COX 2 IOthers:Others: Clofibrate,Cyclophosphamide, Somatostatin
Manisha Sahay
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Manisha sahay
Primary PolydipsiaPsychiatric disorder, thirst with antipsychotics±Hypothalamic lesions No hyponatremia unless intake >10-15 L/d, or
acute 3-4 L water loadUrine osm below 100Rx: Restrict free water ;classically rapid
correction
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Manisha sahay
Reset osmostat
Can excrete water load (10 to 15 mL/kg given orally or intravenously). -excrete more than 80 percent within 4 hours
Mild hyponatremiaNo treatment needed
Manisha Sahay
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Manisha sahay
Beer protomaniaLow Dietary Solute Intake
Elderly, malnourished (“tea and toast” diets) -poor in solutes (Na/K)
Beer drinkers (high water intake, low protein) Pathogenesis
• Minimum urine osmolarity- 60 mosm/l • At least 600-900 msom/kg/d solute load needed to
excrete water >4 l• Beer protomania- daily solute excretion < 250
mosmol /kg, hence maximum urine output can be <4 L day ,if more water ingested -hyponatremia
• Urine appears dilute (osm of< 100)
Rx: NS, increased dietary solute
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Manisha sahay
Exercise associated hyponatremia (EAH)
Clinical features May be severe: cerebral edema, non cardiac PE
Pathogenesis H2O excess; impaired renal H2O excretion Nonosmolar AVP release esp if water in >out
Treatment Limit water to 400-800 ml/h; drink only when
thirsty No role of NS, 3% Nacl if severe
JCEM 2008;93:2072-78
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History & volume status
Serum Osmolality
Urine Osmolality/sp gr
Urine Na
S Cr/urea/K
T3/T4/TSH
CXR
CT Scan Manisha Sahay
Investigations
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Hyponatremia
Low<275True
High>295HyperglycemiaMannitol
N 275-295HyperlipidemiaHyperproteinemia Step 2
Volume
SIADHGC defHypothyroidExercise indPsychogenic
< 20 mmol/lCHFNSCirrhosis
>20 mmol/lCRF
Step3 Urine Na
Extra renalGI loss3rd space loss
RenalSalt wasting dzRTADiureticsCerebral salt wasting
Step 3 Urine Na
Hypovolemic Euvolemia High
Step1 S osmolality
Step 4 U Osm/TSH/GC
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TREATMENT –EUVOLEMIC HYPONATREMIA
Manisha Sahay
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Hyponatremia
Chronic
AsymptomaticSymptomatic
Long term managementTreat etiologyWater restrictionDemeclocyclineUreaV2 receptor antagonist
Some immediate correctionHypertonic saline + FurosemideChange to water restrictionFrequent serum & urine electrolytesDo not exceed 12 meq/l/d
Emergency Hypertonic saline+ furosemide
Acute <48 hrs Chronic>48 hrs
No immediateCorrection needed
Thurman et al,Therapy in nephrology and Hypertension,Saunders 2003
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Manisha sahay
Therapeutic Strategy Euvolemic hyponatremia
Treatment varies with• Presence or Absence of Symptoms• Duration• Magnitude of Hyponatremia• Risk for neurological dz- young, females,
elderly,menstruation
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Acute/Severe/symptomatic hyponatremia
Manisha Sahay
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Manisha sahay
Rate of correction of hyponatremia
Acutesevere (S Na+ <115mmol/L) symptomatic
Hypertonic (3% NaCl)
0.5 mmol/l/hr or 12 mmol/l/dayStop
if convulsions subsideif S Na 120 mEq/L Kumar S, Berl T. The Lancet 1998; 352: 220-8 Adrogue HJ, Madias NE. NEJM 2000; 342: 1581-9
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Manisha sahay
Fluids for correction
Ringer’s = 130 mEq/L0.45%NS = 77 mEq/L3% NaCl- 513 meq/L0.9% NaCl- 154 meq/L
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Manisha sahay
Total correction in 12 hrs = 6 mmol
Volume of infusate needed =
B Wt X 0.6 X Desired increment in Na (120-114) Infusate Na X 1.5
50 kg50X 0.6x6 = 0.23 litre or 230 ml 513X1.5 230 ml in 12 hours19 ml/hr
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Symptomatic/chronichyponatremiaGradual correction
Manisha Sahay
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Manisha sahay
Chronic symptomatic>48 hrs
3% NaCL< 0.5 to 1.0mmol/L per h (<10 to 12mmol/L over first 24h)
Water restriction
Chronic asymptomatic > 48 hoursNo immediate correctionWater restriction
Manisha Sahay
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Manisha sahay
Long term management Euvolemic hyponatremia
Water restriction Free water restriction ,¾ maintenance (1 L/d)
Clozapine -schizophrenic patients with compulsive water drinking
Pharmacological agents (Long-term)Demeclocycline 300 - 600 mg bdUrea 15-60 gm/dLithiumV2 receptor antagonist- Aquaretics
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AVP Receptor antagonists
– •
Mechanism of actionBind to the V2 receptors in renal
collecting tubules/ducts Vasopressin antagonist Uses Euvolemic/ hypervolemic hypo
Na+; Contraindicated in hypovolemia
Chronic hyponatremia not in acute hyponatremia or in
patients with sNa < 115 mmol/L as slow aquaresis Adverse effects: Thirst ; dry mouth
SALT NEJM 2006
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Manisha sahay
Vasopressin Receptor Location & Functions (KI 2006)
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Vasopressin Receptor Antagonists
Tol-vaptan*
Lixi-Vaptan Sata-vaptan
Coni-vaptan
Receptor V2 V2 V2 V1a/V2
Route of administration
Oral Oral Oral IV
Urine Volume
UOSM
24 h Na excretion
No ∆ No ∆ low Dose
High Dose
No ∆ No ∆
*SALT I and SALT II Trials.
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Manisha sahay
CI
Concomitant use of vaptan and potent CYP3A4 inhibitors such as ketoconazole, itraconazole, clarithromycin, ritonavir, or indinavir is contraindicated
Manisha Sahay
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Manisha sahay
Central Pontine MyelinolysisOsmotic demyelination
Pathogenesis• rapid correction / overcorrection of ch hyponatremia. • hypoxic encephalopathy / complication of therapy
Prevention• Adequate oxygenation• Gradual increase in serum sodium level to 120-125 mEq/L.
Symptoms • Dysarthria, dysphagia, seizures, altered mental status,
quadriparesis, hypotension ,locked in syndrome, extrapontine
• Begin 1-3 days after correction of S Na• Irreversible , devastating • MRI diagnostic < 24 h
Risk factors- Hypokalemia, females,alcoholism, liver transplant
Treatment- Relowering S Na - hypotonic fluids, Desmopressin
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SUMMARISING……
Manisha Sahay
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Hyponatremia
Low<275True
High>295HyperglycemiaMannitol
N 275-295HyperlipidemiaHyperproteinemia
Volume
SIADHGC defHypothyroidExercise indPsychogenic
< 20 mmol/lExtrarenalCHFNSCirrhosis
>20 mmol/lRenalCRF
Urine Na
Extra renalGI loss3rd space loss
RenalSalt wasting dzDiureticsCerebral salt wasting
Urine Na
Hypovolemic Euvolemia High
S osmolality
Urine Osm, S Cr,Ur,TSH
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Hyponatremia
AsymptomaticSymptomatic
Long term managementHypertonic saline
Acute <48 hrs
No immediateCorrection neededEmergency
Go slow
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Manisha sahay
Take home message
Hyponatremia –a common, life theatening problem
Step wise evaluation importantInappropriate treatment – Worse
than disease
Practising is the best way of learning!!!
Manisha Sahay
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Manisha sahay
Hope some pieces of puzzle are in place !!
Manisha Sahay